Disorganized cortical thickness covariance network in major depressive disorder implicated by aberrant hubs in large-scale networks

Major depressive disorder is associated with abnormal anatomical and functional connectivity, yet alterations in whole cortical thickness topology remain unknown. Here, we examined cortical thickness in medication-free adult depression patients (n = 76) and matched healthy controls (n = 116). Inter-regional correlation was performed to construct brain networks. By applying graph theory analysis, global (i.e., small-worldness) and regional (centrality) topology was compared between major depressive disorder patients and healthy controls. We found that in depression patients, topological organization of the cortical thickness network shifted towards randomness, and lower small-worldness was driven by a decreased clustering coefficient. Consistently, altered nodal centrality was identified in the isthmus of the cingulate cortex, insula, supra-marginal gyrus, middle temporal gyrus and inferior parietal gyrus, all of which are components within the default mode, salience and central executive networks. Disrupted nodes anchored in the default mode and executive networks were associated with depression severity. The brain systems involved sustain core symptoms in depression and implicate a structural basis for depression. Our results highlight the possibility that developmental and genetic factors are crucial to understand the neuropathology of depression.